In search of hormones and drugs, which stimulate the epidermal cyclic AMP system, we have found four distinct categories: beta-adrenergic agonists, histamine, adenosine and prostaglandins. Each of these receptors becomes unresponsive upon activation (refractoriness). It is presumed that the consequent step after the intracellular cyclic AMP elevation is catalyzed by a type of protein kinases. Our recent studies indicate the presence of several protein kinases in skin, i.e. cyclic AMP-dependent, CA ions-independent and cyclic nucleotide-independent, and also CA ions-dependent. We were unable to detect cyclic GMP-dependent protein kinase in skin after partial purification. Cyclic AMP-dependent protein kinase in skin was studied with special reference to the four known activators of adenylate cyclase. Each of the four stimulators elevates the cyclic AMP level and also activates cyclic AMP dependent protein kinase. Only small amounts of cyclic AMP increases are necessary for its full activation. In contrast to the above receptor systems, no refractoriness was observed for the protein kinase activations. The cyclic AMP stimulators also increased 32P-incorporation into epidermal proteins. A limited number of experiments thus far suggests no abnormality in the protein kinase system in psoriasis, yet further detailed analyses are in progess.